Trifluoroacetic acid → ethyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)carbamate

A solution of tert-butyl (3-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (Example 173A) (300 mg, 0.818 mmol) and DIPEA (0.428 mL, 2.453 mmol) in MeOH (15 mL) at 0° C. (ice bath) was treated with ethyl chloroformate (0.078 mL, 0.818 mmol). The reaction was stirred for 1 hour, then the mixture was concentrated in vacuo. To the residue was added EtOAc (50 ml) and the mixture washed with 0.5M citric acid, sat. NaHCO3, water and brine. The solution was dried over Na2SO4 and solvents removed. To the crude material was added. DCE (5 mL) and TFA (2 mL, 26.0 mmol); the reaction stirred 2 h at 25° C. and solvents removed. The material was diluted with DCM and washed with sat. NaHCO3 and water. The organics dried over Na2SO4 and removed solvent. The material was purified on silica gel 25% EtOAc-DCM to afford ethyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)carbamate (110 mg).

1. concentrationthe mixture was concentrated in vacuo
2. additionTo the residue was added EtOAc (50 ml)
3. washthe mixture washed with 0.5M citric acid, sat. NaHCO3, water and brine
4. dry with materialThe solution was dried over Na2SO4 and solvents
5. customremoved
6. additionTo the crude material was added
7. stirringthe reaction stirred 2 h at 25° C.
8. customsolvents removed
9. additionThe material was diluted with DCM
10. washwashed with sat. NaHCO3 and water
11. dry with materialThe organics dried over Na2SO4
12. customremoved solvent
13. customThe material was purified on silica gel 25% EtOAc-DCM

ORDレコード

ord-cf410f90efaa4be3b7873138dfbb2341

出典データセット

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08940736B2